Comparing restrictive versus liberal oxygen strategies for trauma patients: The TRAUMOX2 trial-Statistical analysis plan.

BACKGROUND: The international advanced trauma life support guidelines recommend that all severely injured trauma patients receive supplemental oxygen based on very limited evidence. The TRAUMOX2 trial randomises adult trauma patients to a restrictive or liberal oxygen strategy for 8 h. The primary composite outcome consists of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome). This manuscript presents the statistical analysis plan for TRAUMOX2. METHODS: Patients are randomised 1:1 in variable block sizes of four, six and eight, stratified by including centre (pre-hospital base or trauma centre) and tracheal intubation at inclusion. The trial will include 1420 patients to be able to detect a 33% relative risk reduction with the restrictive oxygen strategy of the composite primary outcome with 80% power at the 5% significance level. We will conduct modified intention-to-treat analyses on all randomised patients and per-protocol analyses for the primary composite outcome and key secondary outcomes. The primary composite outcome and two key secondary outcomes will be compared between the two allocated groups using logistic regression reported as odds ratios with 95% confidence intervals adjusted for the stratification variables as in the primary analysis. A p-value below 5% will be considered statistically significant. A Data Monitoring and Safety Committee has been established to conduct interim analyses after inclusion of 25% and 50% of the patients. CONCLUSION: This statistical analysis plan of the TRAUMOX2 trial will minimise bias and add transparency to the statistics applied in the analysis of the trial. The results will add evidence on restrictive and liberal supplemental oxygen strategies for trauma patients. TRIAL REGISTRATION: EudraCT number: 2021-000556-19; ClinicalTrials.gov identifier: NCT05146700 (date of registration: 7 December 2021).

Comparing restrictive versus liberal oxygen strategies for trauma patients - the TRAUMOX2 trial: protocol for a randomised clinical trial.

INTRODUCTION: Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma. METHODS AND ANALYSIS: TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial.Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen (>21%) that ensures an SpO2 of 94%. The liberal group receives 12-15 L O2/min or FiO2=0.6-1.0.The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome).With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group. ETHICS AND DISSEMINATION: TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBERS: EudraCT 2021-000556-19; NCT05146700.

Time from injury to arrival at the trauma centre in patients undergoing interhospital transfer.

INTRODUCTION: Trauma patients may require interhospital transfer to definitive care following initial assessment at a primary facility. A prolonged time to transfer may be associated with a poor outcome. The aim of this study was to determine the time from injury to arrival in patients undergoing interhospital transfer to the Trauma Centre at Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. METHODS: Data were obtained from our local trauma registry for the period from 1 November 2016 to 31 October 2019. We included patients who underwent interhospital transfer to our trauma centre. Patients were compared according to a 360-minute time interval between injury and arrival. RESULTS: In the study period, 250 patients underwent interhospital transfer to our trauma centre. The median age was 47 years (interquartile range (IQR) 26-65), the majority were male (68.4%) and a total of 113 patients (46.9%) had an Injury Severity Score (ISS) > 15. The 30-day mortality was 6% (95% confidence interval (CI) 3.6-9.7). The median time from injury to arrival at our trauma centre was 255 minutes (IQR 192-371). We found that 67 patients (27%; 95% CI 21.7-32.6) arrived at our trauma centre more than 360 minutes after time of injury. The patients arriving later than 360 minutes were significantly older (p = 0.004) than the remaining patients. There was no significant difference in the unadjusted 30-day mortality (odds ratio (OR) 1.01, 95% CI 0.3-3.3). CONCLUSIONS: Time from injury to arrival at our trauma centre exceeded 360 minutes for 67 patients (27%) who were significantly older than the remaining patients transferred. FUNDING: departmental funding. TRIAL REGISTRATION: not relevant.

Onset time and duration of action of rocuronium 0.6 mg/kg in patients above 80 years of age: A comparison with young adults.

BACKGROUND: The number of elderly is increasing, and a large proportion of these people will require surgery and anaesthesia. However, little data exist regarding rocuronium in patients above 80 years of age. The aim of this study was to determine the onset time and duration of action for rocuronium 0.6 mg/kg in patients above 80 years compared with young adults. METHODS: This prospective observational study included 16 young (18-40 years) and 16 elderly (>80 years) patients scheduled for total intravenous anaesthesia. Neuromuscular block following rocuronium 0.6 mg/kg was monitored with acceleromyography using train-of-four (TOF) stimulation. The primary outcome was onset time (from administration of rocuronium until TOF count = 0). Secondary outcomes were duration of action (from administration to TOF ratio >0.9) and intubating conditions according to Intubation Difficulty Score. RESULTS: Elderly patients, median age of 84 years, had significantly prolonged onset time compared to younger patients; median 135 seconds (135-158) vs 90 seconds (90-105), respectively, a mean difference of 82 seconds (40-124) and Wilcoxon Mann-Whitney odds (WMW) of 19.48 (7.48-X). Duration of action in elderly patients was significantly longer, with a median time of 81 minute (71-97) vs 53 minute (42-73), respectively, a mean difference of 31 minute (14-48), and WMW odds of 6.35 (2.59-X). There was no significant difference in intubating conditions. CONCLUSIONS: Patients above 80 years had significantly prolonged onset time and duration of action after rocuronium 0.6 mg/kg compared with patients aged 18-40 years.

Hypozincaemia is associated with severity of aneurysmal subarachnoid haemorrhage: a retrospective cohort study.

BACKGROUND: Hypozincaemia may develop in critically ill patients, including those with acute brain injury in the early phase after hospital admission. The aim of this study was to investigate the prevalence of hypozincaemia after aneurysmal subarachnoid haemorrhage (aSAH) and its association with delayed cerebral ischemia and functional outcome. METHODS: We retrospectively analysed a cohort of 384 patients with SAH admitted to the Neurointensive Care Unit at Rigshospitalet, Copenhagen, Denmark, in whom at least one measurement of plasma zinc concentration was done during the hospital stay. Hypozincaemia was defined as at least one measurement of plasma zinc below 10 µmol/L. Potential associations between hypozincaemia, demographic variables and functional outcome after aSAH were analysed in multivariable logistic regression models. RESULTS: Hypozincaemia was observed in 67% (n = 257) of all patients and occurred within 7 days in more than 95% of all hypozincaemic patients. In a multivariable model, severe SAH (WFNS 3-5; OR 4.2, CI 2.21-8.32, p < 0.001) and Sequential Organ Failure Assessment (SOFA) score on the day of admission (OR 1.24, CI 1.11-1.40, p < 0.001) were independently associated with hypozincaemia. In another multivariable model, hypozincaemia was independently associated with an unfavourable outcome (defined as a modified Rankin Scale score from 3 to 6) (OR 1.97, CI 1.06-3.68, p = 0.032), as was age (OR 1.03, CI 1.01-1.05, p = 0.015), SOFA score on the day of admission (OR 1.14, CI 1.02-1.29, p = 0.02), a diagnosis of delayed cerebral ischaemia (OR 4.06, CI 2.29-7.31, p < 0.001) and a clinical state precluding assessment for delayed cerebral ischaemia (OR 15.13, CI 6.59-38.03, p < 0.001). CONCLUSION: Hypozincaemia occurs frequently after aSAH, is associated with a higher disease severity and independently contributes to an unfavourable outcome.